tbuckley/cabot-search huggingface dataset:
Impact of MRI and targeted biopsy on oncological outcomes of prostate cancer after treatment.
Authors: Neha Debnath, Shima Tayebi, Juliana Tobler, Sadhna Verma, Abhinav Sidana
Journal: Journal of Clinical Oncology (2023)

323 Background: To determine the impact of pre-biopsy prostate MRI followed by a targeted biopsy (TBx) approach for initial diagnosis on oncological outcomes after prostate cancer (PCa) treatment. Methods: We performed a retrospective review of all patients who underwent prostate biopsy followed by radiation therapy (RT) or radical prostatectomy (RP) as their first treatment from 2014-2020. Patients were separated into two cohorts based on the diagnostic approach: pre-biopsy prostate MRI during the initial evaluation and those who did not receive MRI. Patients with positive MRI findings underwent a combination of TBx and systematic biopsy (SBx) to confirm the diagnosis, while those without MRI underwent SBx only. Patients with PSA &gt;20 were excluded. Kaplan-Meier curve analysis was used to compare biochemical recurrence (BCR, defined as PSA &gt; 0.2ng/ml after RP or a rise of 2ng/ml after RT) between cohorts. Cox proportional hazard analysis was done to determine the predictors of the BCR. Results: 366 patients (174 diagnosed by SBx only, and 192 diagnosed by pre-biopsy MRI and TBx) with a median follow-up of 40 months were included in the study. 245 men (67%) had RP as their first treatment. Median age and PSA were 64.7 and 7.9, respectively in the SBx cohort and 65.0 and 8.3, respectively in the TBx cohort. There was a significant difference in BCR rate between the TBx (7.98%) versus SBx (19.28%, p&lt;0.05 by log-rank). After adjusting for age, race, PSA, biopsy path, DRE, and family hx, pre-biopsy the MRI and TBx approach for diagnosis was found to be an independent negative predictor (p=0.001); with patients diagnosed with the above approach 71% less likely to have BCR during the study period. Conclusions: Our study shows that patients undergoing pre-biopsy MRI followed by TBx have lower rates of biochemical recurrence compared to men diagnosed without pre-biopsy MRI. To our knowledge, this study is the first to show the positive impact of pre-biopsy MRI on oncological outcomes, likely due to its role in risk stratification, treatment selection, surgical staging, and planning. Further longitudinal studies are needed to discern the true long-term benefits of pre-biopsy MRI on oncological outcomes.
The CONFIDENT-P trial: Clinical implementation of artificial intelligence assistance in prostate cancer pathology.
Authors: Rachel Flach, Nikolas Stathonikos, Tri Nguyen, Natalie D ter Hoeve, Paul J. van Diest, Carmen van Dooijeweert
Journal: Journal of Clinical Oncology (2023)

TPS405 Background: Prostate cancer grading has been subject to variation, putting patients at risk for over- and under-treatment (Flach et al., 2022). As a response, development of artificial intelligence (AI) prostate cancer algorithms has been on the rise in the field of pathology. Despite promising results in retrospective studies, and several FDA-approved and CE-IVD certified algorithms on the market, prospective clinical implementation studies of AI are lacking. Moreover, uptake of digital pathology is currently insufficient due to high implementation costs (Ho et al., 2014). In this trial, we will explore the benefits of an AI-assisted pathology workflow in prostate cancer detection, while maintaining diagnostic safety standards. We will focus on reducing costly immunohistochemistry stains (IHC), which are currently used to aid in the diagnosis of prostate cancer. Methods: CONFIDENT-P is a SPIRIT-AI compliant single-centre, clinical trial, in a fully digital academic pathology laboratory. We will prospectively enroll 80 prostate cancer patients who undergo prostate needle biopsies. The pathology specimens will be pseudo-randomized to be assessed by a pathologist with- or without AI-assistance in a pragmatic (bi-)weekly sequential design, in a 1:1 allocation ratio. Patients are excluded when they are redirected for a second opinion to the UMC Utrecht. In the intervention group, pathologists will assess whole slide images (WSI) of the standard haematoxylin-eosin (HE)-stained sections assisted by the output of a CE-IVD approved prostate cancer detection and grading algorithm. In the control group, pathologists will assess HE WSI according to the current clinical workflow. If no tumour cells are identified or when the pathologist is in doubt, staining by immunohistochemistry (IHC) will be performed. Primary endpoint is the number of saved resources on IHC for detecting tumour cells, since this will clarify tangible cost savings that will help to build the business case for AI. We will compare the proportion of IHC-use in both arms, and calculate adjusted relative risks, using a log-binomial model. The sample size gives at least 80% power to detect a 30% difference in IHC usage, using a one-sided significance level of 5%. Enrolment is set to begin in November 2022. The ethics committee (MREC NedMec) waived the need of official ethical approval, as participants are not subjected to procedures and as they are not required to follow rules. Furthermore, they are not at risk of an inferior diagnosis. Trial registration is therefore applicable nor suitable.
Financial toxicity from first-line TKI plus IO therapies for advanced renal cell carcinoma.
Authors: David Joseph Benjamin, Arash Rezazadeh
Journal: Journal of Clinical Oncology (2023)

634 Background: Since the approval of sunitinib for the treatment of advanced renal cell carcinoma (RCC), the first-line treatment landscape has drastically altered with combination tyrosine kinase inhibitor (TKI) plus immunotherapy (IO) regimens. Despite improvements in survival, it remains unclear if these therapies are cost prohibitive for patients or hospitals compared to prior standard of care sunitinib. Methods: Approved TKI plus IO therapies were identified using the US FDA Oncology Announcements website and confirmed with NCCN Guidelines (Version 3.2023). Cost per unit was identified using public data (Lexicomp or manufacturer’s website). We calculated total cost of each treatment regimen using the cost per unit for each therapy and the median duration on treatment as reported in each combination therapy's clinical trial publication. Results: Average PFS benefit from combination TKI plus IO therapies was 8.1 months (range 4-14.7) in comparison with sunitinib. Average cost of TKI plus IO therapy was $443,839.32 compared with $199,541.44 for sunitinib therapy. Conclusions: Average increase in cost of TKI plus IO therapy compared to sunitinib was $244,297.88. For every month of PFS benefit with TKI plus IO combination therapy, there was on average $30,160.23 cost added per month. These increased costs may be prohibitive for many patients and hospitals, particularly in low- and middle-income countries (LMICs). [Table: see text]
Understanding drivers of treatment preferences in locally advanced or metastatic urothelial carcinoma: A qualitative interview study with patients, caregivers, and physicians.
Authors: Andrea B. Apolo, Nicholas I. Simon, Mallory Farrar, Simrun Grewal, Zsolt Hepp, Lisa Mucha, Christine Michaels-Igbokwe, Sebastian Heidenreich, Katelyn Cutts, John L. Gore
Journal: Journal of Clinical Oncology (2023)

492 Background: The development and selection of treatments for locally advanced or metastatic urothelial carcinoma (la/mUC) have historically focused on clinical outcomes while stakeholder preferences are often considered less frequently. To facilitate the consideration of various perspectives, this study explored factors that may influence preferences of patients, caregivers, and physicians around aspects of la/mUC treatments. Methods: Interview guides elicited perspectives on disease impact (symptoms, health-related quality of life [HRQOL], survival), therapy goals and unmet needs and were conducted with patients with la/mUC, their caregivers, and medical oncologists in the US. Qualitative semi-structured data were collected on symptoms, treatment expectations, and hypothetical treatments that required trade-offs between overall survival (OS), progression-free survival (PFS), cancer pain, and the risk of severe adverse events (SAEs). Participant’s willingness to accept AEs was also explored. Results: Thirty participants, including: 10 patients (mean age 58 years; 60% female, ineligible for cisplatin: 50%), 10 caregivers (mean age 50 years; 70% female), and 10 physicians (mean 17 years treating la/mUC; 30% female) were interviewed. The most frequently reported symptom at diagnosis was pain (patients 90%, caregivers 90%) and blood in urine (physicians 100%). All three groups reported emotional impacts with depression/sadness the most common. Patients (n=7) and caregivers (n=7) relied on physicians for decision-making but felt that alternative treatments were not discussed (patients: n=5; caregivers: n=3). All groups were willing to accept some level of risk of experiencing an AE, but the accepted risk of SAEs varied (patients: 0-50% risk of SAEs; caregivers: 5-100%; physicians: 3-30%). Physicians focused treatment discussions on AEs (n=8), and overall response rate (ORR; n=6), and rarely discussed survival (n=3). All three groups described PFS and treatment response as very or most relevant to them. In the hypothetical choice tasks, all would make trade-offs between OS, PFS, pain reduction and risk of SAEs; consistent with an approach that weighs benefits and risks in treatment selection. Conclusions: Patients likely may benefit from shared, informed decision-making to identify the most appropriate treatment option for them based on clinical outcomes, AEs, HRQOL, and pain control. All groups were willing to make benefit-risk trade-offs but preferences were heterogeneous. While this study included a relatively small number of patients, planned research informed by these results will expand and further identify which treatment attributes are most important to patients.
Intravesical gemcitabine and docetaxel in the treatment of BCG-naïve non–muscle invasive urothelial carcinoma of the bladder: Updates from a phase 2 trial.
Authors: Sunil H. Patel, Andrew Gabrielson, Connie Collins, Nirmish Singla, Trinity Bivalacqua, Noah M. Hahn, Max R. Kates
Journal: Journal of Clinical Oncology (2023)

507 Background: Combination intravesical Gemcitabine and Docetaxel (GEMDOCE) has demonstrated benefit for bacillus Calmette-Guérin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC) in retrospective series and is now being widely utilized as salvage therapy. BCG therapy is fraught with frequent drug shortages and some patients are unable to tolerate BCG due to side effects. Given ongoing BCG shortages as well as the promising efficacy and tolerability of GEMDOCE as a salvage therapy, our objective was to investigate the safety and efficacy of intravesical GEMDOCE for high-risk (HR) BCG-naïve NMIBC in a prospective manner. Methods: This study is an IRB-approved prospective single-arm open-label phase II trial for patients with BCG-naïve HR NMIBC. Intravesical gemcitabine (1,000 mg)/docetaxel (40 mg) in 100mL normal saline is given weekly for 6 weeks as induction followed by monthly maintenance therapy for 2 years among responders. The primary endpoint was 3-month complete response (CR), defined as a negative bladder biopsy 6 weeks after induction treatment. Secondary endpoints included adverse events (AE) and 12-month CR. Results: To date, the study has fully accrued with 25 patients enrolled from July 2020-August 2022. The pre-trial pathologic stages in our cohort were as follows: HGT1 with CIS (n = 7), HGT1 without CIS (n = 6), HGTa (n = 9), and CIS alone (n = 3) (Table). All 25 patients who completed induction therapy demonstrated CR at 3 months. Eight out of 9 (89%) patients with at least 12 months of follow-up demonstrated continued CR. One patient with HGT1 + CIS on enrollment developed a recurrence at 9 months with HGTa. No enrolled patients have undergone radical cystectomy. Grade 1 AEs were common (19/25 patients, 76%) including hematuria, urinary frequency, urgency, and fatigue. Two patients (8%) experienced a Grade 3 AE including urinary retention and UTI requiring hospitalization and intravenous antibiotics. Conclusions: In this ongoing single-arm phase II trial, GEMDOCE appears to be well-tolerated with promising short-term efficacy for patients with BCG-naïve HR NMIBC. [Table: see text]
Clinical results of a phase 1 study of intravesical EG-70 in patients with BCG-unresponsive NMIBC.
Authors: Gary D. Steinberg, Susan J. Kalota, Yair Lotan, Loraine Warner, Shauna Dauphinee, Rosemary Mazanet
Journal: Journal of Clinical Oncology (2023)

512 Background: enGene is developing non-viral gene therapy platforms to deliver nucleic acids (plasmids) to epithelial mucosal tissues such as urothelium of urinary bladder. EG-70 is a nanoparticle formulation of plasmids that activates both innate and adaptive immune responses to activate the immune system within the bladder. The plasmid encodes both IL-12 and activators of the innate immune receptor RIG-I. EG-70 is administered intravesically to elicit local stimulation of anti-tumor immune responses providing durable efficacy in high grade non-muscle invasive bladder cancer (NMIBC) while avoidingsystemic toxicities. Methods: In the Phase 1 study(LEGEND; NCT04752722), escalating doses of EG-70 were administered intravesically to patients with BCG-unresponsive Carcinoma in situ (CIS) NMIBC on weeks 1 and 2 or weeks 1, 2, 5, 6 of 12-week treatment cycle. At the week 12 assessment, patients with stable disease (SD) or complete response (CR), as assessed by urine cytology, cystoscopy, and bladder biopsy, were allowed electively to remain on EG-70 for up to 3 additional 12-week cycles. Results: To date, 19 patients have been treated. There have been no DLTs. AEs (48 GR1, 17 GR 2 and 1 GR3) have been largely consistent with urinary tract instrumentation, and were not dose related. Eighteen patients have completed one cycle of EG-70, and 67% have achieved CR. Fifteen patients with CR or SD at the end of cycle 1 elected to receive additional treatment cycles (continuation rate of 15/18 ( 83%)). Durable CRs were seen at all dose levels. Patients who receive additional cycles are followed for durability of response (Table). Complete Response. Conclusions: These results demonstrate the safety, tolerability and durable therapeutic potential of intravesical EG-70 in patients with BCG-unresponsive CIS. A Phase 2 study will proceed in 2023. Clinical trial information: NCT04752722 . [Table: see text]
Patient opinions on controversies: In regard to low-risk prostate cancer, is Gleason 6 the old Gleason 5?
Authors: Howard Wolinsky, James Schraidt, Mark Lichty, Philip Segal, Alejandro Berlin, Mohummad Minhaj Siddiqui, Samuel L. Washington, Herbert M. Geller
Journal: Journal of Clinical Oncology (2023)

329 Background: In 2005, the International Society of Urologic Pathology effectively eliminated Gleason patterns 1 and 2, thus removing Gleason grades 2-5 as a cancer diagnosis. Today, patients with low-risk Gleason 6 prostate cancer, prostate cancer clinicians, guideline writers, and policymakers are facing issues about whether Gleason 6 lesions should be reclassified as noncancer. Some of the issues being discussed among urologists, radiation oncologists, and pathologists focus on whether to reclassify low-risk Gleason 6 prostate lesions as a noncancer with the goal of reducing patient anxiety and financial toxicity. We also asked about biopsy methods, which affects both the low-risk and favorable intermediate-risk populations, that have been a major topic in support organizations over the past two years. We conducted this survey of patients on active surveillance to determine where patients stand on these issues to help guide clinicians, policymakers, and guideline writers. Methods: We conducted a survey in October 2022 asking patients their views on these issues. We invited patients on active surveillance or previously on active surveillance for low-risk prostate cancer to respond to a 40-question survey to share their views on a range of topics related to the diagnosis of Gleason grade 6 lesions as cancer, as well as complementary issues related to innovations in biopsy and active surveillance. We had access to email lists containing ~2,500 names from the AnCan Foundation’s Active Surveillance Virtual Support Group, Active Surveillance Patients International, Prostate Cancer Support Canada, and The Active Surveillor newsletter. Other major prostate cancer support groups also distributed links to the questionnaire posted on SurveyMonkey. Results: At the deadline for placeholders for abstracts, the survey is underway. Questions for patients include: Have you experienced distress (anxiety or depression) because of the cancer label from Gleason 6? Have you experienced financial toxicity, including cancellation of insurance policies or an increase in rates, because of the cancer diagnosis? If Gleason 6 was reclassified as a noncancer, would you stop surveillance? What will you prefer as a next biopsy--transperineal to avoid the risk of sepsis and other infections or transrectal which may cause less immediate pain? Conclusions: We intend that the results will inform decision making as to the classification of Gleason 6 diagnoses.
Consideration for reclassification of pathologically upstaged T3a renal cell carcinomas.
Authors: Dhruv Puri, Luke Wang, Margaret F Meagher, Aastha Shah, Saeed Ghassemzadeh, Franklin Liu, Mimi Nguyen, Sohail Dhanji, Kevin Hakimi, Ryan Nasseri, Juan Javier-Desloges, Rana R. McKay, Ithaar H Derweesh
Journal: Journal of Clinical Oncology (2023)

644 Background: Pathological upstaging to pT3a disease can occur after the surgical treatment of clinical T1 and T2 Renal Cell Carcinomas (RCCs), and this upstaging has been previously shown to be associated with poorer outcomes. With an intent to delve deeper into the disparateness in outcomes of pT3a disease, we investigated the survival of patients with an initial clinical stage of cT1, cT2 and cT3a. Methods: Using the National Cancer Database (NCDB), patients with RCC were categorized by pathological and clinical staging of RCC according to the American Joint Committee on Cancer Guidelines (AJCC). The primary outcome was measured as overall survival (OS) at the end of follow up. Five-year survival rates and Kaplan-Meier Analysis assessed the differences between cT1 → pT3a, cT2 → pT2, cT2 → pT3a, and cT3a → pT3a. Multivariable cox regression (MVA) assessed predictors OS with age, sex, ethnicity, Charlson Score, socioeconomic status, geography, tumor size histology and grade, lymph node metastasis, surgical margins, and surgery type (partial versus radical nephrectomy) as covariates. Results: 53908 patients were analyzed (10789 cT1 → pT3a, 22183 cT2 → pT2, 9676 cT2 → pT3a, 11260 cT3a → pT3a, mean follow up 62.3 months). Of all pT3a patients, 64.5% were upstaged from cT1-2. MVA for OS demonstrated Hispanic ethnicity to be protective (hazard ratio [HR]=0.88, P&lt;0.001) and revealed different histologic risks. MVA for OS demonstrated that cT2 → pT3a (HR=1.33, P&lt;0.001, cT1 → pT3a [ref]) and cT3a → pT3a (HR=1.35, P&lt;0.001, cT1 → pT3a [ref]) were associated with worsened OS, and that cT1 → pT3a and cT2 → pT2 (HR=0.96, P&lt;0.052, cT1 → pT3a [ref]) were associated with improved OS. Kaplan-Meier analysis revealed a difference in 5 year overall survival as well (cT1→pT3a 72%, cT2→pT2 77%, cT2→pT3a 61%, and cT3a→pT3a 59%, p &lt; 0.001). Conclusions: Patients with cT1 upstaged to pT3a have similar outcomes to cT2 staged to pT2 and better outcomes than cT2 upstaged with the latter’s outcomes being more like cT3a staged to pT3a. The TNM staging system from AJCC for RCCs should consider these outcomes and adjust the grouping for RCCs accordingly.
Practice patterns and predictors of treatment intensification in patients with metastatic castration-sensitive prostate cancer.
Authors: Geoffrey T. Gotto, Steven M. Yip, Bobby Shayegan, Dylan E. O'Sullivan, Christopher J.D. Wallis, Naveen S. Basappa, Ilias Cagiannos, Robert James Hamilton, Cristiano Ferrario, Ricardo Fernandes, Brita Danielson, Fred Saad, Sebastien J. Hotte, Darren R. Brenner, Winson Y. Cheung, Devon J. Boyne, Katherine Chan, Brendan Osborne, Anousheh Zardan, Shawn Malone
Journal: Journal of Clinical Oncology (2023)

76 Background: In recent years, treatment intensification beyond androgen deprivation therapy (ADT) with several novel therapies have shown survival benefit in patients with metastatic castration-sensitive prostate cancer (mCSPC). Given the rapidly evolving landscape in mCSPC treatment, there is a need to better understand how treatment strategies fit in real-world clinical practice and are combined/sequenced with other available therapies. Methods: Using electronic medical records and administrative data, a population-based retrospective cohort study was conducted. Patients aged ≥18 years of age who were newly diagnosed with de novo mCSPC and initiated ADT post-diagnosis between 2010 to 2020 in Alberta, Canada, were included. Treatment intensification was defined as the receipt of apalutamide, abiraterone acetate, enzalutamide, or chemotherapy (e.g. docetaxel) within 180 days of ADT initiation. Results: A total of 2,515 de novo mCSPC were identified during study period with 2,098 (83%) patients initiating ADT post-diagnosis. Of those, 525 (25%) received intensification beyond ADT. The percentage of patients who were intensified was 3% in 2010-2013 and gradually increased to 67% in 2020. Between 2014-2017, docetaxel was the most common therapy for intensification, but its use decreased considerably in 2018-2020 with abiraterone acetate, apalutamide and enzalutamide becoming increasingly available in the mCSPC setting. Upon progression, 46% and 22% in the intensified group versus 38% and 13% in the ADT-alone group initiated one and two-lines of subsequent therapies respectively. Abiraterone acetate and enzalutamide were the most common subsequent therapy for both the intensified (32% and 31% respectively) and the ADT-alone (56% and 38% respectively) groups. Docetaxel (24%) was used as subsequent therapy among mCSPC patients who were intensified with oral systemic agents. In multivariable logistic regression analyses of patients diagnosed in 2014-2020, significant predictors of intensification were younger age at diagnosis, lower Charlson comorbidity index, greater number of metastatic sites, shorter time to ADT initiation, referral to a specialists/cancer centres, surgery or radiation prior to ADT, and more recent year of diagnosis (all p&lt;0.05). Conclusions: In Alberta, Canada, there has been a considerable increase in the utilization of ADT intensification therapies that correspond with the timing of clinical trial data and approvals of novel agents. Early referral to specialists/cancer centres is warranted to intensify mCSPC treatment beyond ADT and to improve patients’ outcomes. [Table: see text]